14-77406038-C-G

Variant names:

• chr14-77406038-C-G
• NM_001113475.3:c.780G>C
• NOXRED1 p.Gln260His

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001113475.3(NOXRED1):​c.780G>C​(p.Gln260His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NOXRED1 NM_001113475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 0 publications found

Genes affected

NOXRED1 (HGNC:20487): (NADP dependent oxidoreductase domain containing 1) Predicted to enable pyrroline-5-carboxylate reductase activity. Predicted to be involved in L-proline biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33200374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOXRED1	NM_001113475.3	MANE Select	c.780G>C	p.Gln260His	missense	Exon 5 of 6	NP_001106946.1	Q6NXP6-1
	NOXRED1	NM_001394980.1		c.780G>C	p.Gln260His	missense	Exon 6 of 7	NP_001381909.1	Q6NXP6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOXRED1	ENST00000380835.7	TSL:1 MANE Select	c.780G>C	p.Gln260His	missense	Exon 5 of 6	ENSP00000370215.2	Q6NXP6-1
	NOXRED1	ENST00000555901.1	TSL:2	n.1535G>C		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.17
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Benign	0.12	T
Sift4G	Benign	0.12	T
Varity_R		0.10
gMVP		0.47
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-77872381;